Developmental stress and social phenotypes : integrating neuroendocrine, behavioural and evolutionary perspectives

The social world is filled with different types of interactions, and social experience interacts with stress on several different levels. Activation of the neuroendocrine axis that regulates the response to stress can have consequences for innumerable behavioural responses, including social decision-making and aspects of sociality, such as gregariousness and aggression. This is especially true for stress experienced during early life, when physiological systems are developing and highly sensitive to perturbation. Stress at this time can have persistent effects on social behaviours into adulthood. One important question remaining is to what extent these effects are adaptive. This paper initially reviews the current literature investigating the complex relationships between the hypothalamic-pituitary-adrenal (HPA) axis and other neuroendocrine systems and several aspects of social behaviour in vertebrates. In addition, the review explores the evidence surrounding the potential for ‘social programming’ via differential development and activation of the HPA axis, providing an insight into the potential for positive effects on fitness following early life stress. Finally, the paper provides a framework from which novel investigations could work to fully understand the adaptive significance of early life effects on social behaviours.PostprintPeer reviewe

Modifications of glucocorticoid receptors mRNA expression in the hypothalamic‐pituitary‐adrenal axis in response to early-life stress in female Japanese quail

The present study was funded by a BBSRC David Phillips Research Fellowship to KAS.Stress exposure during early‐life development can programme individual brain and physiology. The hypothalamic‐pituitary‐adrenal (HPA) axis is one of the primary targets of this programming, which is generally associated with a hyperactive HPA axis, indicative of a reduced negative‐feedback. This reduced feedback efficiency usually results from a reduced level of the glucocorticoid receptor (GR) and/or the mineralocorticoid receptor (MR) within the HPA axis. However, a few studies have shown that early‐life stress exposure results in an attenuated physiological stress response, suggesting an enhance feedback efficiency. In the present study, we aimed to determine whether early‐life stress had long‐term consequences on GR and MR levels in quail and whether the effects on the physiological response to acute stress observed in prenatally stressed individuals were underpinned by changes in GR and/or MR levels in one or more HPA axis components. We determined GR and MR mRNA expression in the hippocampus, hypothalamus and pituitary gland in quail exposed to elevated corticosterone during prenatal development, postnatal development, or both, and in control individuals exposed to none of the stressors. We showed that prenatal stress increased the GR:MR ratio in the hippocampus, GR and MR expression in the hypothalamus and GR expression in the pituitary gland. Postnatal stress resulted in a reduced MR expression in the hippocampus. Both early‐life treatments permanently affected the expression of both receptor types in HPA axis regions. The effects of prenatal stress are in accordance with a more efficient negative‐feedback within the HPA axis and thus can explain the attenuated stress response observed in these birds. Therefore, these changes in receptor density or number as a consequence of early‐life stress exposure might be the mechanism that allows an adaptive response to later‐life stressful conditions.Publisher PDFPeer reviewe

Glucocorticoid programming of neuroimmune function

Work attributed to the ideas presented within this manuscript was supported by the BBSRC (Biotechnology and Biological Sciences Research Council, UK) under the EASTBIO doctoral training program [grant no. BB/J01446X/1], awarded to DJW. KAS was also part funded by a BBSRC grant [no. BB/L002264/1].Throughout life physiological systems strive to maintain homeostasis and these systems are susceptible to exposure to maternal or environmental perturbations, particularly during embryonic development. In some cases, these perturbations may influence genetic and physiological processes that permanently alter the functioning of these physiological systems; a process known as developmental programming. In recent years, the neuroimmune system has garnered attention for its fundamental interactions with key hormonal systems, such as the hypothalamic pituitary adrenal (HPA) axis. The ultimate product of this axis, the glucocorticoid hormones, play a key role in modulating immune responses within the periphery and the CNS as part of the physiological stress response. It is well-established that elevated glucocorticoids induced by developmental stress exert profound short and long-term physiological effects, yet there is relatively little information of how these effects are manifested within the neuroimmune system. Pre and post-natal periods are prime candidates for manipulation in order to uncover the physiological mechanisms that underlie glucocorticoid programming of neuroimmune responses. Understanding the potential programming role of glucocorticoids may be key in uncovering vulnerable windows of CNS susceptibility to stressful experiences during embryonic development and improve our use of glucocorticoids as therapeutics in the treatment of neurodegenerative diseases.Publisher PDFPeer reviewe

Egg-laying substrate selection for optimal camouflage by quail

Camouflage is conferred by background matching and disruption, which are both affected by microhabitat [1]. However, microhabitat selection that enhances camouflage has only been demonstrated in species with discrete phenotypic morphs [2 and 3]. For most animals, phenotypic variation is continuous [4 and 5]; here we explore whether such individuals can select microhabitats to best exploit camouflage. We use substrate selection in a ground-nesting bird (Japanese quail, Coturnix japonica). For such species, threat from visual predators is high [6] and egg appearance shows strong between-female variation [7]. In quail, variation in appearance is particularly obvious in the amount of dark maculation on the light-colored shell [8]. When given a choice, birds consistently selected laying substrates that made visual detection of their egg outline most challenging. However, the strategy for maximizing camouflage varied with the degree of egg maculation. Females laying heavily maculated eggs selected the substrate that more closely matched egg maculation color properties, leading to camouflage through disruptive coloration. For lightly maculated eggs, females chose a substrate that best matched their egg background coloration, suggesting background matching. Our results show that quail “know” their individual egg patterning and seek out a nest position that provides most effective camouflage for their individual phenotyp

Long-term effects of adolescent stress on neophobic behaviors in zebra finches are modulated by social context when in adulthood

Funding was provided by a BBSRC Research Fellowship to KAS and a University of St Andrews postgraduate scholarship to MGE.Experiencing stress during adolescence can increase neophobic behaviors in adulthood, but most tests have been conducted in the absence of conspecifics. Conspecifics can modulate responses to stressors, for example by acting as ‘social buffers’ to attenuate the aversive appraisal of stressors. Here, we investigate the long-term effects of adolescent stress on the behavioral responses to novel stimuli (a mild stressor) across social contexts in an affiliative passerine bird, the zebra finch. During early (days 40–60) or late (days 65–85) adolescence the birds (n = 66) were dosed with either saline or the hormone corticosterone (CORT). CORT was given in order to mimic a physiological stress response and saline was given as a control. In adulthood, the birds' behavioral responses to a novel environment were recorded in both the presence and absence of conspecifics. An acute CORT response was also quantified in adolescence and adulthood. Our findings show clear evidence of social context mediating any long-term effects of adolescent stress. In the presence of familiar conspecifics no treatment effects were detected. Individually, birds dosed with CORT in early adolescence were slower to enter a novel environment, spent more time perching in the same novel environment, and, if female, engaged in more risk assessment. Birds dosed in late adolescence were unaffected. No treatment effects were detected on CORT, but adolescents had a higher CORT concentration than adults. Our results are the first to suggest that familiar conspecifics in adulthood can buffer the long-term effects of stress that occurred during early adolescence.Publisher PDFPeer reviewe

Group housing during adolescence has long-term effects on the adult stress response in female, but not male, zebra finches (Taeniopygia guttata)

Funding was provided by a BBSRC David Phillips Research Fellowship to KAS and a University of St Andrews postgraduate scholarship to MGE.Adolescent social interactions can have long-term effects on physiological responses to stressors in later-life. A larger adolescent group size can result in higher stressor-induced secretion of glucocorticoids in adulthood. The effect may be due to a socially-mediated modulation of gonadal hormones, e.g. testosterone. However, group size (number of animals) has been conflated with social density (space per animal). Therefore it is hard to determine the mechanisms through which adolescent group size can affect the stress response. The current study aimed to tease apart the effects of group size and social density during adolescence on the physiological stress response and gonadal hormone levels in adulthood. Adolescent zebra finches were housed in groups varying in size (2 vs. 5 birds per cage) and density (0.03m3 vs. 0.06m3 per bird) during early adolescence (day 40-60). Density was only manipulated in birds raised in groups of five. Glucocorticoid concentration secreted in response to a standard capture and restraint stressor was quantified in adolescence (day 55±1) and adulthood (day 100+). Basal gonadal hormones concentrations (male testosterone, female estradiol) were also quantified in adulthood. Female birds housed in larger groups, independent of social density, secreted a higher glucocorticoid concentration 45 mins into restraint regardless of age, and had higher peak glucocorticoid concentration in adulthood. Adult gonadal hormone concentrations were not affected by group size or density. Our results suggest that group size, not density, is a social condition that influences the development of the endocrine response to stressors in female zebra finches, and that these effects persist into adulthood. The findings have clear relevance to the social housing conditions necessary for optimal welfare in captive animals, but also elucidate the role of social rearing conditions in the emergence of responses to stressors that may persist across the lifespan and affect fitness of animals in wild populations.Publisher PDFPeer reviewe

Eggshell appearance does not signal maternal corticosterone exposure in Japanese quail:an experimental study with brown-spotted eggs

Reproduction is a critical period for birds as they have to cope with many stressful events. One consequence of an acute exposure to stress is the release of corticosterone, the avian stress hormone. Prolonged stress can have negative impacts on the immune system, resulting in, for example, increased oxidative stress. Through maternal effects, females are known to modulate their investment in eggs content according to their own physiological condition. Less is known about maternal investment in eggshells, especially in pigments. The two main eggshell pigments may possess opposite antioxidant properties: protoporphyrin (brown) is a pro-oxidant, whereas biliverdin (blue-green) is an antioxidant. In Japanese quail, we know that the deposition of both pigments is related to female body condition. Thus, a chronic stress response may be reflected in eggshell coloration. Using female Japanese quails that lay brown-spotted eggs, we explored whether physiological exposure to corticosterone induces a change in female basal stress and antioxidant factors, and eggshell pigment concentration, spectrophotometric reflectance, and maculation coverage. We supplemented adult females over a 2 week period with either peanut oil (control) or corticosterone (treatment). We collected pre- and post-supplementation eggs and analysed the effect of corticosterone treatment on female physiology and eggshell appearance parameters. Except for corticosterone-fed birds which laid eggs with brighter spots, supplementation had no significant effect on female physiology or eggshell pigment concentration, reflectance and maculation. The change in eggshell spot brightness was not detected by a photoreceptor noise-limited color opponent model of avian visual perception. Our data confirms that eggshell reflectance in spotted eggs varies over the laying sequence, and spot reflectance may be a key factor that is affected by females CORT exposure, even if the changes are not detected by an avian visual model

Social experience during adolescence in female rats increases 50 kHz ultrasonic vocalizations in adulthood, without affecting anxiety-like behavior

Funding was provided by a University of St Andrews postgraduate studentship to MGE.Adolescents are highly motivated to engage in social interactions, and researchers have hypothesized that positive social relationships during adolescence can have long term, beneficial effects on stress reactivity and mental well‐being. Studies of laboratory rodents provide the opportunity to investigate the relationship between early social experiences and later behavioral and physiological responses to stressors. In this study, female Lister‐hooded rats (N = 12 per group) were either (a) provided with short, daily encounters (10 min/day) with a novel partner during mid‐adolescence (postnatal day 34–45; “social experience,” SE, subjects) or (b) underwent the same protocol with a familiar cagemate during mid‐adolescence (“control experience,” CE, subjects), or (c) were left undisturbed in the home cage (non‐handled “control,” C, subjects). When tested in adulthood, the groups did not differ in behavioral responses to novel environments (elevated plus maze, open field, and light‐dark box) or in behavioral and physiological (urinary corticosterone) responses to novel social partners. However, SE females emitted significantly more 50 kHz ultrasonic vocalizations than control subjects both before and after social separation from a familiar social partner, which is consistent with previous findings in male rats. Thus, enhanced adolescent social experience appears to have long‐term effects on vocal communication and could potentially modulate adult social relationships.PostprintPeer reviewe

ESUR guidelines for MR imaging of the sonographically indeterminate adnexal mass: an algorithmic approach

A significant proportion of adnexal masses detected by sonography are indeterminate. Either their organ of origin is uncertain or it is unclear whether their nature is benign or malignant. MR imaging of the sonographically indeterminate adnexal mass can resolve most of these uncertainties. Most indeterminate masses result from common benign conditions and women with such masses can avoid unnecessary or inappropriate surgery. For the minority of women whose masses are malignant, use of MR imaging rather than a ‘wait and watch’ strategy of repeat ultrasound (US) results in a more timely diagnosis. There are simple diagnostic steps in the MR imaging assessment which direct an algorithmic and problem-solving approach based on signal characteristics and morphology. MR imaging should provide a more timely diagnosis and, thereby, guide the management of the patient with reduced costs of investigation and treatment

Peri-pubertal exposure to testicular hormones organizes response to novel environments and social behaviour in adult male rats

Funding was received from the Wellcome Trust ISSF (grant ID 097831/Z/11/Z) scheme, awarded to the University of St Andrews.Previous research has shown that exposure to testicular hormones during the peri-pubertal period of life has long-term, organizational effects on adult sexual behaviour and underlying neural mechanisms in laboratory rodents. However, the organizational effects of peri-pubertal testicular hormones on other aspects of behaviour and brain function are less well understood. Here, we investigated the effects of manipulating peri-pubertal testicular hormone exposure on later behavioural responses to novel environments and on hormone receptors in various brain regions that are involved in response to novelty. Male rodents generally spend less time in the exposed areas of novel environments than females, and this sex difference emerges during the peri-pubertal period. Male Lister-hooded rats (Rattus norvegicus) were castrated either before puberty or after puberty, then tested in three novel environments (elevated plus-maze, light–dark box, open field) and in an object/social novelty task in adulthood. Androgen receptor (AR), oestrogen receptor (ER1) and corticotropin-releasing factor receptor (CRF-R2) mRNA expression were quantified in the hypothalamus, hippocampus and medial amygdala. The results showed that pre-pubertally castrated males spent more time in the exposed areas of the elevated-plus maze and light–dark box than post-pubertally castrated males, and also confirmed that peri-pubertal hormone exposure influences later response to an opposite-sex conspecific. Hormone receptor gene expression levels did not differ between pre-pubertally and post-pubertally castrated males in any of the brain regions examined. This study therefore demonstrates that testicular hormone exposure during the peri-pubertal period masculinizes later response to novel environments, although the neural mechanisms remain to be fully elucidated.Publisher PDFPeer reviewe